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Drought stress is the most important abiotic factor limiting upland rice yields. Identification of quantitative trait loci (QTL) conferring improved drought resistance may facilitate breeding progress. We previously mapped a QTL with a large effect on grain yield under severe drought stress (qtl12.1) in the Vandana/Way Rarem population. In the current paper, we present results from a series of experiments investigating the physiological mechanism(s) by which qtl12.1 affects grain yield under drought conditions. We performed detailed plant water status measurements on a subset of lines having similar crop growth duration but contrasting genotypes at qtl12.1 under field (24 genotypes) and greenhouse (14 genotypes) conditions. The Way Rarem-derived allele of qtl12.1 was confirmed to improve grain yield under drought mainly through a slight improvement (7%) in plant water uptake under water-limited conditions …